title: Activity motifs reveal principles of timing in  transcriptional control of the yeast metabolic network.
abstract: Significant insight about biological networks arises from the study of network motifs--overly abundant network subgraphs--but such wiring patterns do not specify when and how potential routes within a cellular network are used. To address this limitation, we introduce activity motifs, which capture patterns in the dynamic use of a network. Using this framework to analyze transcription in Saccharomyces cerevisiae metabolism, we find that cells use different timing activity motifs to optimize transcription timing in response to changing conditions: forward activation to produce metabolic compounds efficiently, backward shutoff to rapidly stop production of a detrimental product and synchronized activation for co-production of metabolites required for the same reaction. Measuring protein abundance over a time course reveals that mRNA timing motifs also occur at the protein level. Timing motifs significantly overlap with binding activity motifs, where genes in a linear chain have ordered binding affinity to a transcription factor, suggesting a mechanism for ordered transcription. Finely timed transcriptional regulation is therefore abundant in yeast metabolism, optimizing the organism's adaptation to new environmental conditions.
authors.affiliation: Department of Computer Science, Stanford University, Stanford, California 94305, USA.
authors.forename: Gal
authors.initials: G
authors.lastname: Chechik
authors.forename: Eugene
authors.initials: E
authors.lastname: Oh
authors.forename: Oliver
authors.initials: O
authors.lastname: Rando
authors.forename: Jonathan
authors.initials: J
authors.lastname: Weissman
authors.forename: Aviv
authors.initials: A
authors.lastname: Regev
authors.forename: Daphne
authors.initials: D
authors.lastname: Koller
mesh_terms: D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005990:Glycerol / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D010427:Pentose Phosphate Pathway; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D005990:Glycerol